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Background: In patients with infectious diseases, remote consultation (RC) may be questionable compared with face-to-face office consultation (OC), not only because of the lack of physical examination but also because of the risk of overprescribing antibiotics (ATBs). Aim: To analyse ATB prescription in OC versus RC in a sample of French GPs. Design & setting: This is a retrospective observational cohort study in general practice in 2021. Anonymised data were collected from voluntary GPs. Method: The influence of the mode of consultation on ATB prescription was analysed using a χ² test. A secondary multivariate analysis investigated the factors influencing the use of OC or RC in patients who received at least one ATB. Results: In total, 35 503 consultations with an identifiable rating were included, corresponding to seven doctors' activities, practising with five locums and three residents. ATBs were prescribed in 10.41% of RCs and 6.77% of OCs (P

This paper introduces the finding of mural burials in building A, Cerro de las Monjas sector, at Marcahuamachuco archaeological site. Building A is part of a set of multifamily residences. A description and analysis of bone remains is made. Finally, according with ethnographical data, we suggest the role of the buried individuals’ souls as guardians and protectors of the buildings and their occupants.

Abstract Background Epidemiological studies on risk factors for colorectal cancer (CRC) have mainly focused on diet, and being overweight is now recognized to contribute significantly to CRC risk. Overweight and obesity are defined as an excess of adipose tissue mass and are associated with disorders in lipid metabolism. Peroxisome proliferator-activated receptors (PPARs) and retinoid-activated receptors (RARs and RXRs) are important modulators of lipid metabolism and cellular homeostasis. Alterations in expression and activity of these ligand-activated transcription factors might be involved in obesity-associated diseases, which include CRC. Cyclooxygenase-2 (COX-2) also plays a critical role in lipid metabolism and alterations in COX-2 expression have already been associated with unfavourable clinical outcomes in epithelial tumors. The objective of this study is to examine the hypothesis questioning the relationship between alterations in the expression of nuclear receptors and COX-2 and the weight status among male subjects with CRC. Method The mRNA expression of the different nuclear receptor subtypes and of COX-2 was measured in 20 resected samples of CRC and paired non-tumor tissues. The association between expression patterns and weight status defined as a body mass index (BMI) was statistically analyzed. Results No changes were observed in PPARγ mRNA expression while the expression of PPARδ, retinoid-activated receptors and COX-2 were significantly increased in cancer tissues compared to normal colon mucosa (P ≤ 0.001). The weight status appeared to be an independent factor, although we detected an increased level of COX-2 expression in the normal mucosa from overweight patients (BMI ≥ 25) compared to subjects with healthy BMI (P = 0.002). Conclusion Our findings show that alterations in the pattern of nuclear receptor expression observed in CRC do not appear to be correlated with patient weight status. However, the analysis of COX-2 expression in normal colon mucosa from subjects with a high BMI suggests that COX-2 deregulation might be driven by excess weight during the colon carcinogenesis process.

Background Immune checkpoint inhibitors (ICI) have transformed cancer treatment over the last decade. Alongside this therapeutic improvement, a new variety of side effects has emerged, called immune-related adverse events (irAEs), potentially affecting any organ. Among these irAEs, myocarditis is rare but life-threatening.Methods We conducted a multicenter cross-sectional retrospective study with the aim of better characterizing ICI-related myocarditis. Myocarditis diagnosis was based on the recent consensus statement of the International Cardio-Oncology Society.Results Twenty-nine patients were identified, from six different referral centers. Most patients (55%) were treated using anti-programmed-death 1, rather than ICI combination (35%) or anti-programmed-death-ligand 1 (10%). Transthoracic echocardiography was abnormal in 52% of them, and cardiac magnetic resonance showed abnormal features in 14/24 patients (58%). Eleven patients (38%) were classified as severe. Compared with other patients, they had more frequently pre-existing systemic autoimmune disease (45% vs 6%, p=0.018), higher troponin level on admission (42-fold the upper limit vs 3.55-fold, p=0.001), and exhibited anti-acetylcholine receptor autoantibodies (p=0.001). Seven patients (24%) had myocarditis-related death, and eight more patients died from cancer progression during follow-up. Twenty-eight patients received glucocorticoids, 10 underwent plasma exchanges, 8 received intravenous immunoglobulins, and 5 other immunosuppressants. ICI rechallenge was performed in six patients, with only one myocarditis relapse.Discussion The management of ICI-related myocarditis may be challenging and requires a multidisciplinary approach. Prognostic features are herein described and may help to allow ICI rechallenge for some patients with smoldering presentation, after an accurate evaluation of benefit–risk balance.

Background & Aims: β-catenin is a well-known effector of the Wnt pathway, and a key player in cadherin-mediated cell adhesion. Oncogenic mutations of β-catenin are very frequent in paediatric liver primary tumours. Those mutations are mostly heterozygous, which allows the co-expression of wild-type (WT) and mutated β-catenins in tumour cells. We investigated the interplay between WT and mutated β-catenins in liver tumour cells, and searched for new actors of the β-catenin pathway. Methods: Using an RNAi strategy in β-catenin-mutated hepatoblastoma (HB) cells, we dissociated the structural and transcriptional activities of β-catenin, which are carried mainly by WT and mutated proteins, respectively. Their impact was characterised using transcriptomic and functional analyses. We studied mice that develop liver tumours upon activation of β-catenin in hepatocytes (APCKO and β-cateninΔexon3 mice). We used transcriptomic data from mouse and human HB specimens, and used immunohistochemistry to analyse samples. Results: We highlighted an antagonistic role of WT and mutated β-catenins with regard to hepatocyte differentiation, as attested by alterations in the expression of hepatocyte markers and the formation of bile canaliculi. We characterised fascin-1 as a transcriptional target of mutated β-catenin involved in tumour cell differentiation. Using mouse models, we found that fascin-1 is highly expressed in undifferentiated tumours. Finally, we found that fascin-1 is a specific marker of primitive cells including embryonal and blastemal cells in human HBs. Conclusions: Fascin-1 expression is linked to a loss of differentiation and polarity of hepatocytes. We present fascin-1 as a previously unrecognised factor in the modulation of hepatocyte differentiation associated with β-catenin pathway alteration in the liver, and as a new potential target in HB. Impact and implications: The FSCN1 gene, encoding fascin-1, was reported to be a metastasis-related gene in various cancers. Herein, we uncover its expression in poor-prognosis hepatoblastomas, a paediatric liver cancer. We show that fascin-1 expression is driven by the mutated beta-catenin in liver tumour cells. We provide new insights on the impact of fascin-1 expression on tumour cell differentiation. We highlight fascin-1 as a marker of immature cells in mouse and human hepatoblastomas.

Aim: Diverting stomas are routinely used in restorative surgery following total mesorectal exicision (TME) for rectal cancer to mitigate the clinical risks of anastomotic leakage (AL). However, routine diverting stomas are associated with their own complication profile and may not be required in all patients. A tailored approach based on personalized risk of AL and selective use of diverting stoma may be more appropriate. The aim of the TAilored SToma policY (TASTY) project was to design and pilot a standardized, tailored approach to diverting stoma in low rectal cancer. Method: A mixed‐methods approach was employed. Phase I externally validated the anastomotic failure observed risk score (AFORS). We compared the observed rate of AL in our cohort to the theoretical, predicted risk of the AFORS score. To identify the subset of patients who would benefit from early closure of the diverting stoma using C‐reactive protein (CRP) we calculated the Youden index. Phase II designed the TASTY approach based on the results of Phase I. This was evaluated within a second prospective cohort study in patients undergoing TME for rectal cancer between April 2018 and April 2020. Results: A total of 80 patients undergoing TME surgery for rectal cancer between 2016 and 2018 participated in the external validation of the AFORS score. The overall observed AL rate in this cohort of patients was 17.5% (n = 14). There was a positive correlation between the predicted and observed rates of AL using the AFORS score. Using ROC curves, we calculated a CRP cutoff value of 115 mg/L on postoperative day 2 for AL with a sensitivity of 86% and a negative predictive value of 96%. The TASTY approach was designed to allocate patients with a low risk AFORS score to primary anastomosis with no diverting stoma and high risk AFORS score patients to a diverting stoma, with early closure at 8–14 days, if CRP values and postoperative CT were satisfactory. The TASTY approach was piloted in 122 patients, 48 (39%) were identified as low risk (AFORS score 0–1) and 74 (61%) were considered as high risk (AFORS score 2–6). The AL rate was 10% in the low‐risk cohort of patient compared to 23% in the high‐risk cohort of patients, p = 0.078 The grade of Clavien‐Dindo morbidity was equivalent. The incidence of major LARS was lowest in the no stoma cohort at 3 months (p = 0.014). Conclusion: This study demonstrates the feasibility and safety of employing a selective approach to diverting stoma in patients with a low anastomosis following TME surgery for rectal cancer. [ABSTRACT FROM AUTHOR]

Huacas de Moche -también conocido como Huacas del Sol y de la Luna-, es uno de los sitios icónicos de la arqueología andina. Tradicionalmente, el conocimiento científico y popular asocia el sitio con la cultura Mochica, o Moche. Se afirma que, entre los años 100 y 850 d.C., Huacas de Moche fue una ciudad que concentró el poder de un Estado que influyó ideológica y políticamente en la costa norte peruana. No obstante, los restos arqueológicos de este antiguo asentamiento de barro indican que eso es solo una parte de la historia, puesto que el sitio fue ocupado por grupos culturalmente diferentes, antes y después de los mochicas, a lo largo de aproximadamente dos mil años. El presente artículo describe y analiza la historia ocupacional de Huacas de Moche a partir de la evidencia arqueológica disponible, haciendo énfasis en los períodos poco conocidos, examinando, además, cómo durante esas fases de ocupación estas comunidades fueron modificando el paisaje natural y cultural.

Abstract Background CAPARFI study explored whether sonoelastographic data collected using the acoustic radiation force impulse (ARFI) system are reliable when evaluating skeletal muscles and whether the technique can detect muscle changes with aging. Methods Twenty young (YH; 18–30 years) and 30 old (OH; ≥70 years) healthy volunteers and 15 old patients with cancer (OP; ≥70 years) were assessed through quantitative ARFI measurements (m s−1) of the relaxed rectus femoris, tibialis anterior, and soleus muscles, and Short Physical Performance Battery (SPPB) test. The reliability in ARFI measurements was evaluated by intra‐class correlation coefficient. Among‐group differences in ARFI measurements and SPPB were evaluated using a global linear model. Results Acoustic radiation force impulse measurements demonstrated high reliability in all groups (intra‐class correlation coefficient > 0.82). ARFI measurements of the rectus femoris muscle were significantly lower in both the OH and OP groups than in the YH group (1.46 ± 0.12 and 1.50 ± 0.32 vs. 1.80 ± 0.35 m s−1). The ARFI measurements of the soleus muscle were significantly lower in the OP group than in the YH group (1.37 ± 0.37 vs. 1.70 ± 0.53 m s−1). No significant difference was observed for tibialis anterior muscle. Significantly lower SPPB scores were observed in the OP group (10.3 ± 1.4 out of 12) than in the YH (12.0 ± 0.0) and OH groups (11.5 ± 1.0). Conclusions This study demonstrated that ARFI quantitative measurements are reliable in relaxed skeletal muscle and may be reliably used to explore muscle changes with aging and/or neoplasia in clinical practice.

Abstract Background Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [11C]-PBR28 and [18F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [18F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [18F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [11C]-PBR28. Results All in vitro sections showed specific binding of [18F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [11C]-PBR28 or [18F]-PBR06 was negative in all participants. Conclusion Despite good uptake on surgical samples in vitro, [11C]-PBR28 and [18F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease. Trial registration: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov .

Background: In patients with infectious diseases, remote consultation (RC) may be questionable compared with face-to-face office consultation (OC), not only because of the lack of physical examination but also because of the risk of overprescribing antibiotics (ATBs). Aim: To analyse ATB prescription in OC versus RC in a sample of French GPs. Design & setting: This is a retrospective observational cohort study in general practice in 2021. Anonymised data were collected from voluntary GPs. Method: The influence of the mode of consultation on ATB prescription was analysed using a χ² test. A secondary multivariate analysis investigated the factors influencing the use of OC or RC in patients who received at least one ATB. Results: In total, 35 503 consultations with an identifiable rating were included, corresponding to seven doctors' activities, practising with five locums and three residents. ATBs were prescribed in 10.41% of RCs and 6.77% of OCs (P<0.01). RC was associated with more frequent prescription of ATBs for respiratory and ear, nose, and throat (ENT) viral infections and urinary tract infections. For patients aged 20–40 years, ATB prescription was more associated with RC. Conclusion: RC is associated with a more frequent ATB prescription than OC, mostly for patients aged 20–40 years, who are most likely to use new technologies; and for urinary tract infections or respiratory and ENT viral infections. Further studies on RC outcomes should be conducted to better analyse the impact of RC on the prescribing of ATBs. [ABSTRACT FROM AUTHOR]